Journal
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
Volume 20, Issue 4, Pages 330-334Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MED.0b013e3283631809
Keywords
cabergoline; Cushing's disease; mifepristone; pasireotide
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Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH
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Purpose of reviewRecently developed agents treat Cushing's disease by inhibiting ACTH secretion from corticotrope tumors or antagonizing cortisol action.Recent findingsThe dopamine agonist cabergoline and the somatostatin agonist pasireotide target ACTH secretion. Each has low rates of normalization of urine-free cortisol (UFC), about 40% at doses of 1-7mg weekly and 20% at doses of 600 or 900g twice daily, respectively. Cabergoline, an oral agent, has a relatively benign side-effect profile, primarily asthenia. Small trials suggest that combination therapy with ketoconazole increases effectiveness. Pasireotide, a parenteral agent, is associated with types and rates of adverse events similar to those seen with other somatostatin agonists (diarrhea, nausea, cholelithiasis), except for glucose intolerance, which occurs more frequently (approximate to 75%). It may be most effective when UFC is less than two-fold normal. A few case reports suggest that pasireotide or cabergoline may control tumor size and ACTH secretion from macroadenomas. Retinoic acid must be evaluated further. The glucocorticoid antagonist mifepristone ameliorates glucose intolerance but may not normalize other Cushingoid features.SummaryThese novel approaches provide options for treatment of patients in whom surgery has failed or is not possible, and those who decline adrenalectomy or radiation therapy.
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